Ask about this productRelated genes to: GPR75 antibody
- Gene:
- GPR75 NIH gene
- Name:
- G protein-coupled receptor 75
- Previous symbol:
- -
- Synonyms:
- WI-31133
- Chromosome:
- 2p16.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-10-22
- Date modifiied:
- 2016-10-05
Related products to: GPR75 antibody
Related articles to: GPR75 antibody
- Hyperuricemia-related vascular endothelial injury is closely associated with hypertension, atherosclerosis, and other cardiovascular diseases. Although GPR75 has been implicated in vascular inflammation and hypertension, whether it mediates hyperuricemia-induced endothelial dysfunction and how it is regulated upstream remain unknown. - Source: PubMed
Publication date: 2026/08/07
Fu JiawuHe JunbingLi KeshenZhang MantingLi JiekaiLiu YuchunChen YusenBi Wei - Bronchopulmonary dysplasia (BPD), a debilitating chronic respiratory condition afflicting preterm neonates, stems from oxidative injury and is characterized by arrested alveolar growth and aberrant inflammatory responses. This investigation uncovers a novel mechanistic axis in which the 20-hydroxyeicosatetraenoic acid (20-HETE)/GPR75 signaling cascade acts as a previously unrecognized driver of NLRP1 inflammasome activation in neonatal BPD, thereby linking oxidative stress to inflammatory signaling via p53. Using murine hyperoxia models, we observe that excessive oxygen exposure selectively upregulates GPR75 expression and 20-HETE biosynthesis within alveolar epithelial cells. Genetic inactivation of Gpr75 in vivo significantly attenuated hyperoxia-induced lung injury, oxidative stress, and NLRP1-dependent secretion of interleukin-1β and interleukin-18. Mechanistic dissection revealed that 20-HETE induces NLRP1 inflammasome assembly in rat alveolar epithelia via p53-mediated signaling. In vitro corroboration via lentiviral-mediated Gpr75 silencing, with scrambled shRNA serving as a negative control, further validated its role in hyperoxia-triggered NLRP1 activation and cytokine release (P < 0.01 vs. scrambled control). Collectively, these findings establish the 20-HETE/GPR75 axis as a critical regulator of inflammasome-dependent pathogenesis in BPD. Blockade of this axis inhibits inflammasome assembly and downstream inflammation by suppressing p53 signaling. These results highlight this axis as a promising therapeutic target to mitigate oxygen-induced injury and inflammatory sequelae in preterm infants. - Source: PubMed
Xu QiuXiangTian XiaoLiLi BinKang Jian - Mitochondrial dysfunction plays a crucial role in retinal ganglion cells (RGCs) injury, the early pathogenesis of diabetic retinopathy (DR). G protein-coupled receptor 75 (GPR75), an orphan receptor, is a novel regulator of metabolic diseases. However, the role and mechanisms of GPR75 underlying diabetic RGCs mitochondrial dysfunction have not been reported. To investigate the function of GPR75, we knockdown the receptor in streptozotocin (STZ) mice and high glucose (HG)-treated primary RGCs. Our investigations revealed an upregulation of GPR75 in DR. Furthermore, we demonstrated that GPR75 knockdown could mitigate the progression of DR, with its protective effects associated with the inhibition of mitochondrial dysfunction in RGCs. Adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), a regulator of mitochondrial function and a cellular energy sensor, was identified as a novel target of GPR75. Immunofluorescence and co-immunoprecipitation (CO-IP) analyses confirmed the co-localization and interaction between GPR75 and AMPK in RGCs. Mechanistically, the upregulation of GPR75 inhibits AMPK-mediated mitochondrial homeostasis, resulting in impaired mitochondrial dynamics, disrupted energy metabolism, and elevated reactive oxygen species (ROS), which ultimately trigger pyroptosis and apoptosis in RGCs. Notably, the AMPK-activator AICAR mitigates GPR75-induced mitochondrial dysfunction, pyroptosis, and apoptosis. In summary, our findings suggest that the targeted inhibition of GPR75 may represent a promising therapeutic strategy for DR. - Source: PubMed
Publication date: 2026/07/15
Liu MengrenCheng XueLiu WenqiangYu HongDanYu ShengxueWang YaliChen XinyuanMiao QuanlingYuan YirongDai WeiHu JiaweiZhang NaSui JiahengLiu XuezhengZuo Zhongfu - G-protein-coupled receptor 75 (GPR75) has emerged as an important mediator in diet-induced obesity (DIO) and a promising therapeutic target for anti-obesity drugs. However, the anatomical location of GPR75 in the brain remains unclear, hindering the understanding of GPR75 biology in DIO. Here, we generated a new GPR75-GFP-Ires-Cre knockin mouse strain, in which the Cre expression is driven by the endogenous GPR75 promoter and the GFP is fused with the C-terminal of the GPR75 protein. Both Cre and GFP were confirmed to be colocalized with the endogenous GPR75 expression. In addition, the GPR75-GFP fusion protein remains functionally normal with unaltered susceptibility to DIO. Moreover, using this mouse strain, we found that GPR75 is broadly expressed throughout the brain and mainly localized to the cytoplasm of brain neurons. This new genetic tool can therefore be used to study the neural basis for GPR75 in mediating DIO. - Source: PubMed
Publication date: 2026/06/02
Wheeler Emma CYang RunzhouFarmer Stephen MZhang ShengZhang NingyanAn ZhiqiangTong Qingchun - Progression of ischemic heart disease to acute coronary syndrome (ACS) is fueled by endothelial dysfunction and disruptions in vascular signaling pathways. The relationship between the angiotensin-converting enzyme 2 (ACE2)/renin-angiotensin system (RAS) axis and eicosanoid metabolism is still not fully understood. This study aimed to investigate whether changes in circulating ACE2 and 20-hydroxyeicosatetraenoic acid (20-HETE) reflect dysregulation of a combined ACE2/RAS-eicosanoid axis in ACS and to evaluate the diagnostic and functional significance of 20-HETE. We studied 122 patients with ischemic heart disease (including stable coronary artery disease (SCAD) and ACS) and 54 controls. Levels of circulating ACE2 and 20-HETE were measured using ELISA. Additionally, in vitro experiments with cell culture models were conducted to evaluate how pharmacological modulation of the ACE2/RAS axis affects nitric oxide (NO) production, inflammatory signaling, and CYP4F2 expression. Both ACE2 and 20-HETE levels were significantly lower in ACS compared to SCAD and controls (p < 0.001). Circulating 20-HETE effectively distinguished ACS from SCAD with an AUC of 0.91. In endothelial cells, altering the ACE2/RAS axis impacted NO availability and inflammatory gene expression, correlating with changes in CYP4F2 levels. 20-HETE affected cellular metabolic activity and GPR75 signaling, indicating a functional connection between RAS signaling and eicosanoid pathways. Lower circulating 20-HETE levels are associated with disruption of the integrated ACE2/RAS-eicosanoid axis, which is linked to endothelial dysfunction in ACS. These results suggest that 20-HETE may serve not only as a biomarker but also as part of a broader vascular signaling network related to acute coronary instability. - Source: PubMed
Publication date: 2026/06/10
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